Development of pH-activatable fluorescent probes for rapid visualization of metastatic tumours and fluorescence-guided surgery via topical spraying

A series of pH-activatable aza-BODIPY-based fluorescent probes were developed for rapid cancer visualization and real-time fluorescence-guided surgery by harnessing topical spraying. These probes exhibited good water-solubility, a tunable pK_a from 5.0 to 7.9, and stable intense NIR emission at ∼725 nm under acidic conditions. AzaB5 with a pK_a value of 6.7 was able to rapidly and clearly visualize pulmonary and abdominal metastatic tumours including tiny metastases less than 2 mm via topical spraying, further improving intraoperative fluorescence-guided resection. We believe that AzaB5 is promising as a powerful tool to rapidly delineate a broad range of malignancies and assist surgical tumour resection.